Dysfunctional decision making can have devastating impacts on individuals and on society. Many types of decision making are therefore under vigorous investigation. This proposal emphasizes value-based decisions, in which the chooser selects among options based on his subjective assessment of their value. A deeper understanding of this behavior will help to develop the best possible treatments for decision making disorders, including the many forms of addiction and the cognitive deficits that accompany mental illness, brain injury, and neurodegenerative disease. Consumer choice is one of the best studied forms of value-based decisions. Economists, in collaboration with geneticists, have found that our economic our personalities have a significant genetic basis, but it is difficult to trace causal links between genes and behavior in humans. To overcome this problem, many geneticists turn to simpler invertebrate organisms like the nematode worm C. elegans which has many of the same genes as humans and in which gene function is much easier, cheaper, and faster to study. But evidence that nematodes are capable of value-based decision making, in a scientifically meaningful sense, has been lacking. Economists have developed rigorous testing procedures for determining whether subjective value is the deciding factor in an organism's decisions. In preliminary research for this proposal, the PI's laboratory developed microfluidic devices that enable this test to be done on nematodes based on food choices. The tests show that nematodes are sensitive to the quality and price of food in a manner fully consistent with value-based decision making. The proposed research lays the cornerstone for a multiphase R01-level project that defines the neural circuit for value-based decision making in nematodes and exploits this knowledge to investigate the functional interactions of human genes known to be associated with economic decisions. The research begins by developing a new, high-throughput assay for measuring the subjective value of food options in populations of foraging nematodes. The proposed assay utilizes an innovative method for fabricating miniature radial arm mazes. Each arm of the maze will be baited with a unique food option defined in terms of the concentration of edible bacteria and a naturally occurring repellent secreted by pathogenic bacteria. We will use this approach to determine how information about food and repellents is represented by neuronal activity, and how these representations are combined to control behavior. Next, we will begin the processes of identifying the decision making circuit using a genetic approach to create nematode strains in which only one of the five food-detecting sensory neurons is functional. Sensory neurons sufficient to drive decision making will be considered to be the input neurons of the circuit. This knowledge will accelerate the search for the rest of the neurons in the circuit in future R01-level research.
A person's health and welfare depend on making decisions that are in his or her best interest, but the neuronal mechanisms of decision making are poorly understood. The proposed research develops innovative methods to streamline behavioral and neurophysiological analyses of decision making in a model organism whose genes can be manipulated directly, quickly, and inexpensively. Successful completion of the proposed research will establish a new model system in which to assess the function of networks of human genes associated with complex behavioral traits.
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